Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 987
Filtrar
1.
Medicina (B Aires) ; 81(2): 293-296, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-33906151

RESUMO

The congenial form of junctional ectopic tachycardia is a rare variant of pediatric tachyarrhythmia that due to its incessant nature and its refractoriness to the traditionally used antiarrhythmic agents has a high morbimortality The clinical cases of two patients with a diagnosis of congenital junctional ectopic tachycardia with inadequate response to the regular pharmacological options, who developed dilated cardiomyopathy and ventricular dysfunction secondary to sustained tachycardia, are presented. In both ivrabadine, a new innovative option was used with excellent clinical response.


Assuntos
Taquicardia Ectópica de Junção , Antiarrítmicos/uso terapêutico , Criança , Eletrocardiografia , Humanos , Ivabradina/uso terapêutico , Taquicardia Ectópica de Junção/tratamento farmacológico
2.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809359

RESUMO

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.


Assuntos
Basigina/genética , Ciclofilina A/genética , Infarto do Miocárdio/tratamento farmacológico , Proteína 1 Associada à Membrana da Vesícula/genética , Animais , Biomarcadores/metabolismo , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Ivabradina/farmacologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Suínos
4.
Kardiologiia ; 60(10): 33-37, 2020 Oct 10.
Artigo em Russo | MEDLINE | ID: mdl-33228503

RESUMO

Aim      To evaluate the effect of combination ivabradine-containing therapy for chronic heart failure (CHF) with preserved ejection fraction on quality of life (QoL) and the primary composite endpoint during a one-year follow-up.Material and methods  This study included 160 patients aged 45 to 65 years with NYHA functional class (FC) II-III CHF with preserved left ventricular ejection fraction (CHF-PEF) and grade I and II diastolic dysfunction associated with FC III stable angina with sinus rhythm and a heart rate (HR) higher than 70 bpm. Presence of CHF-PEF was confirmed by results of echocardiography and myocardial tissue Doppler imaging. During one year of prospective observation, effects of bisoprolol and ivabradine as a part of the combination therapy on the primary composite endpoint, including death from cardiovascular complications (CVC) and hospitalizations for myocardial infarction (MI) or CHF, were evaluated in patients with CHF-PEF. Patients were randomized to three groups: A, bisoprolol with dose titration from 2.5 to 10 mg; В, combination of bisoprolol 2.5-10 mg and ivabradine 10-15 mg/day; and С, ivabradine 10-15 mg/day. All patients were on a chronic background therapy, including angiotensin-converting enzyme inhibitors (lisinopril) or, if not tolerated, angiotensin II receptor blockers (valsartan), antiaggregants, statins (atorvastatin, rosuvastatin), and short-acting nitrates as required. If edema developed diuretics were added. The follow-up duration was one year.Results After 12 weeks of follow-up, the achievement of goal HR in group A was associated with a tendency to increased distance in the 6-min walk test from 279±19 to 341±21 m (р>0,05); in group B the distance increased from 243±25 to 319±29 m (р<0.05); and in group C the distance increased from 268±21 to 323±22 m (р<0.05). In the combination ivabradine and bisoprolol treatment group, results of the 24-h electrocardiogram monitoring showed a more pronounced anti-ischemic effect associated with a decrease in the number of myocardial ischemic episodes (p<0.05). QoL was evaluated with the Minnesota questionnaire against the background of treatment. At 12 weeks of observation, the total score decreased from 44.5±2.6 to 38.4±2.1 in group A; from 45±2.9 to 38±2.2 in group B; and from 50.9±3.2 to 42.7±2.8 in group C (р<0.05). The risk of acute MI and repeated hospitalization for CHF during the year of observation, as evaluated according to the Kaplan-Meier method, decreased in both bisoprolol and ivabradine combination treatment groups.Conclusion      The inclusion of bisoprolol and ivabradine into the background therapy of CHF-PEF patients with stable IHD provided an improvement of QoL and a decrease in the risk of hospitalization for acute MI and CHF during the year of observation.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Idoso , Benzazepinas , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca , Humanos , Ivabradina , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 382-385, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018008

RESUMO

An elevated heart rate (HR) often persists in resuscitated septic shock patients, increasing the risk of mortality. Several drugs for HR control, such as esmolol and ivabradine, have been tested in the recent years, but their benefit on the overall cardiovascular system is still under investigation. The aim of this study is to investigate the hemodynamic effects of the two drugs in a protocol of polymicrobial septic shock and resuscitation, mainly focusing on the vascular function. Twelve pigs were divided into three experimental groups: the esmolol-treated group (n=4), the ivabradine-treated group (n=5) and the control group (n=3). The characteristic arterial time constant τ was computed on aortic arterial pressure (AoP), together with estimates of total arterial compliance and peripheral resistance. Power spectral analysis of aortic and radial diastolic BP oscillations was performed to estimate the sympathetic autonomic control of vascular tone. Septic shock induced a severe cardiac and vascular disarray, only partially resolved by resuscitation. The administration of esmolol, but not ivabradine, was beneficial both for cardiac and vascular function, thereby its adjunction to standard therapies could help to improve patient's condition and optimize the resuscitation strategies.Clinical Relevance-This study shows a potential beneficial effect of esmolol on the arterial tree.


Assuntos
Propanolaminas , Choque Séptico , Animais , Humanos , Ivabradina , Propanolaminas/farmacologia , Choque Séptico/tratamento farmacológico , Suínos , Taquicardia/tratamento farmacológico
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2756-2759, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018577

RESUMO

Persisting tachycardia is often observed in resuscitated septic shock patients, and it is an independent risk factor for increased mortality. Recently, several drugs, such as esmolol and ivabradine, have been proved to be beneficial in HR control, but their overall impact on cardiac functions needs further investigation. The aim of this study is to study the effects of the two drugs on heart function in a protocol of polymicrobial septic shock and resuscitation. Twelve pigs were divided into three experimental groups: the esmolol-treated group (n=4), the ivabradine-treated group (n=5) and the control group (n=3). Cardiac autonomic activity was estimated by heart rate variability (HRV) indices and baroreflex sensitivity (BRS). The Buckberg index was adopted to evaluate myocardial oxygenation efficiency. Septic shock induced a severe autonomic dysfunction and a lower cardiac efficiency, not resolved by fluids resuscitation. The administration of the drugs improved both the HRV and the BRS, but this favourable condition was preserved after noradrenaline administration only in the esmolol group. The interaction of esmolol with the autonomic system is beneficial in septic shock to restore an improved condition of HRV and control, while ivabradine is not as effective when administered in adjunction to noradrenaline.


Assuntos
Propanolaminas , Choque Séptico , Animais , Humanos , Ivabradina/uso terapêutico , Propanolaminas/uso terapêutico , Choque Séptico/tratamento farmacológico , Suínos , Taquicardia/tratamento farmacológico
7.
Actas esp. psiquiatr ; 48(5): 228-232, sept.-oct. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-198425

RESUMO

No disponible


Bullous skin lesions with eccrine gland necrosis have been repeatedly described in drug-induced coma, while similar cutaneosus changes in patients with non-drugin-duced coma have only rarely been reported. We present one comatose patients with bullous skin lesión and eccrine gland necrosis on the dependent part of the body. These findings suggest that the hyperthermia, coupled with hy-poxia and local pressure could cause sweat gland fatigue and degeneration


Assuntos
Humanos , Masculino , Idoso , Ideação Suicida , Overdose de Drogas/complicações , Dermatopatias Vesiculobolhosas/induzido quimicamente , Transtornos da Personalidade/psicologia , Dermatopatias Vesiculobolhosas/patologia , Ivabradina/envenenamento , Ramipril/envenenamento , Trazodona/envenenamento , Alprazolam/envenenamento
8.
Int Heart J ; 61(5): 1044-1048, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921663

RESUMO

Ivabradine is a selective inhibitor of the sinoatrial node "funny" current, prolonging the slow diastolic depolarization. As it has the ability to block the heart rate selectively, it is more effective at a faster heart rate. It is recommended for the treatment of heart failure reduced ejection fraction in the presence of beta-blocker therapy for the further reduction of the heart rate. However, previous reports have shown the association of Torsade de pointes (TdP) with concurrent use of ivabradine and drugs resulting in QT prolongation or blockage of the metabolic breakdown of ivabradine. In this article, we report two cases of patients with heart failure reduced ejection fraction who developed TdP after ivabradine use. Our report highlights the need to exercise caution with the administration of ivabradine in the presence of a reduced repolarization reserve, such as QT prolongation or metabolic insufficiency.


Assuntos
Fármacos Cardiovasculares/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/efeitos adversos , Torsades de Pointes/induzido quimicamente , Antagonistas Adrenérgicos beta/efeitos adversos , Interações Medicamentosas , Cardioversão Elétrica , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Volume Sistólico
9.
Clin Ter ; 171(5): e449-e453, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32901791

RESUMO

Ivabradine (IVA) is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. This pure heart rate-lowering agent possesses well-documented antianginal and anti-ischemic properties comparable to well-established antianginal agents, such as ß-blockers and calcium channel blockers. IVA lowers heart rate (HR) without affecting contractility or vascular tone and it is licensed for HR control in chronic heart diseases. The heart rate reduction is beneficial in patients with coronary artery disease (CAD), chronic stable angina pectoris, and chronic heart failure (CHF). Published trials documented not only pharmacodynamic and pharmacokinetic properties but also acceptable tolerance and safety profile of IVA, compared to other currently used cardiovascular drugs, including betablockers. The aim of this review is to describe recent evidences with IVA an interesting medicament, able to lower HR by selective inhibition of the If current, and to describe its applications.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/uso terapêutico , Angina Estável/tratamento farmacológico , Doença Crônica , Humanos
10.
Kardiologiia ; 60(6): 1135, 2020 Jul 07.
Artigo em Russo | MEDLINE | ID: mdl-32720615

RESUMO

Aim To study the antianginal and heart rate slowing effects in patients with stable angina (SA) who failed to achieve the heart rate (HR) goal and were switched from the beta-blocker (BB) metoprolol tartrate to a combination of metoprolol tartrate and ivabradine.Materials and methods The study included 54 patients with SA not higher than functional class (FC) III (35 (64.8 %) men and 19 (35.2 %) women) aged 59 [48; 77] years. Prior to the study start and at 4 and 8 weeks of follow-up, electrocardiography (ECG) and 24-h ECG monitoring (24h-ECGM) were performed for all patients. The follow-up period duration was 8 weeks. The antianginal and heart rate slowing effects of therapy were clinically evaluated by a decrease in frequency of anginal attacks and patients' requirement for nitrates, a decrease in HR, and the effect on 24h-ECGM indexes characterizing myocardial ischemia. At the first stage, all patients were prescribed metoprolol tartrate (Egilok®, Egis, Hungary) 25 mg twice a day. Patients with resting HR still higher than 70 bpm after 4 weeks of treatment were switched from metoprolol tartrate to a fixed ivabradine/metoprolol combination (Implicor®, Servier, France) 5 / 25 mg twice a day. Thus, based on achieving/ non-achieving the HR goal, two groups of patients were formed. Statistical analysis was performed with a STATISTICA 10,0 software package.Results After 4 weeks of therapy with metoprolol tartrate 25 mg twice a day, 18 (33.3%) patients of group 1 achieved the HR goal of 70 bpm, while  36 (66.7%) patients of group 2 did not achieve the goal. For further correction of HR, patients of group 2 were switched from metoprolol tartrate to ivabradine/metoprolol 5 / 25 mg twice a day. After 4 weeks of the ivabradine/metoprolol treatment, 31 (86.1 %) patients achieved the HR goal with median resting HR of 62 [56; 70] bpm. The number of angina attacks decreased from 6 [3; 8] to 2 [1; 3] per week (р<0.001). 24hECGM showed that the mean diurnal HR decreased from 81 [76; 96] to 66 [56; 76] bpm (р<0.001); mean night HR decreased from 69 [73; 80] to 52 [43; 60] bpm (р=0.012); and the ischemic ST segment depression was absent.Conclusion Only 33.3% of patients with stable angina achieved the HR goal on metoprolol tartrate 25 mg twice a day. Supplementing the beta-blocker metoprolol tartrate at the same dose with ivabradine allowed 86.1% of patients to achieve the HR goal and exerted a pronounced anti-anginal effect.


Assuntos
Angina Estável , Antagonistas Adrenérgicos beta , Idoso , Quimioterapia Combinada , Feminino , Frequência Cardíaca , Humanos , Ivabradina , Masculino , Metoprolol , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Ther Adv Cardiovasc Dis ; 14: 1753944720934937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32611276

RESUMO

Ivabradine is a pure heart-rate lowering drug that is nowadays used, accordingly to the last ESC Guidelines, to reduce mortality and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction and in symptomatic patiens with inappropriate sinus tachycardia. Moreover, interesting effect of ivabradine on endothelial and myocardial function and on oxidative stress and inflamation pathways are progressively emerging. The aim of this paper is to highlight newer evidences about ivabradine effect (and consequently possible future application of the drug) in pathological settings different from guidelines-based clinical practice.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Ivabradina/uso terapêutico , Animais , Função Atrial/efeitos dos fármacos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Ivabradina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos
12.
PLoS One ; 15(7): e0236193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692755

RESUMO

BACKGROUND: Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints. METHODS: We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes. RESULTS: Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 ×10-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61). CONCLUSION: Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.


Assuntos
Ivabradina/farmacologia , Modelos Genéticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Alelos , Doenças Cardiovasculares/fisiopatologia , Determinação de Ponto Final , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/genética , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Proteínas Musculares/genética , Canais de Potássio/genética , Fatores de Risco
14.
Rev. esp. cardiol. (Ed. impr.) ; 73(5): 368-375, mayo 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194544

RESUMO

INTRODUCCIÓN Y OBJETIVOS: La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA). MÉTODOS: Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24 h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ovario de hámster chino transfectadas con el ADN que codifica la expresión de los distintos canales que componen dicho potencial de acción, registrando las corrientes iónicas mediante la técnica del parche de membrana. RESULTADOS: Se obtendrá información tanto del efecto de la ivabradina en las corrientes iónicas y el potencial de acción del NAV como de su eficacia y su seguridad en pacientes con FA permanente. CONCLUSIONES: Los resultados del proyecto BRAKE-AF podrían permitir que la ivabradina se incluyera en el limitado arsenal de fármacos disponibles actualmente para el control de frecuencia en la FA


INTRODUCTION AND OBJECTIVES: Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS: A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS: New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS: The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF


Assuntos
Humanos , Animais , Feminino , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Ivabradina/farmacologia , Fibrilação Atrial/tratamento farmacológico , Fármacos Cardiovasculares/farmacologia , Digoxina/farmacologia , Antiarrítmicos/farmacologia , Técnicas de Patch-Clamp , Potenciais de Ação , Fibrilação Atrial/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos
15.
Front Biosci (Schol Ed) ; 12: 161-172, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114453

RESUMO

Coronary artery disease (CAD) and heart failure (HF) are major worldwide threat to health and well-being. Important progress in the treatment of CAD and HF have contributed to a decline in mortality around the world. A considerable number of epidemiological studies reported a strong independent association between elevated heart rate and major cardiovascular risk factors including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine (IVA) is a pure heart rate-lowering agent with well-documented anti-anginal and anti-ischemic properties comparable to well-established anti-anginal agents, such as beta-blockers and calcium channel blockers. The heart rate reduction with IVA is beneficial in patients with CAD, chronic stable angina pectoris, and chronic HF, with an acceptable tolerance and safety profile. The pharmacodynamic and pharmacokinetic properties of this drug make it an important agent in the management of patients with CAD and HF. The aim of this short review is to explore recent results with IVA, a new medication that lowers heart rate by selectively inhibiting the If current, and to describe others future potential applications.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Ivabradina/uso terapêutico , Animais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Br J Anaesth ; 124(6): 726-738, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32147100

RESUMO

BACKGROUND: Ivabradine lowers heart rate (HR) without affecting contractility or vascular tone. It is licensed for HR control in chronic heart diseases. We performed a systematic review and meta-analyses to examine whether ivabradine could decrease major adverse cardiovascular events (MACE) and mortality in critically ill patients. METHODS: We searched Medline, Embase, Cochrane Library, and Web of Science for RCTs. Trial quality was assessed using the Cochrane risk of bias tool. Random-effects meta-analyses were performed if at least three trials or 100 patients were available. Results are reported as weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs). Trial sequential analyses were performed to estimate the sample size needed to reach definitive conclusions of efficacy or futility. RESULTS: We included 13 RCTs (n=1497 patients). We found no evidence of an impact of ivabradine on MACE (three RCTs, 819 patients; OR=0.77; 95% CI, 0.53-1.11) or mortality (10 RCTs, 1356 patients; OR=1.07; 95% CI, 0.63-1.82), but sample sizes were not reached to allow definitive conclusions. Compared with placebo or standard care, ivabradine reduced HR (eight RCTs, 464 patients; WMD, -9.5 beats min-1; 95% CI, -13.3 to -5.8). Risk of bradycardia was not different between ivabradine and control (five RCTs, 434 patients; OR=1.2; 95% CI, 0.60-2.38). Risk of bias was overall high or unclear. CONCLUSIONS: Ivabradine reduces HR compared with placebo or standard care. The effect on MACE or mortality in acute care remains unclear. Further RCTs powered to detect changes in clinically relevant outcomes are warranted. CLINICAL TRIAL REGISTRATION: Prospero CRD42018086109.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Cardiopatias/tratamento farmacológico , Cardiopatias/mortalidade , Ivabradina/uso terapêutico , Estado Terminal , Cardiopatias/fisiopatologia , Humanos , Resultado do Tratamento
17.
Am Heart J ; 223: 98-105, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32217365

RESUMO

BACKGROUND: Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. METHODS: PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated ß-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, ß-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). RESULTS: Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean -10.0 beats/min, 95% CI -15.7 to -4.3 vs 0.7 beats/min, 95% CI -5.4 to 6.7, P = .011). Patient-reported outcomes, ß-blocker use/dose, and safety events were similar (all P > .05). CONCLUSIONS: Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing ß-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/uso terapêutico , Alta do Paciente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Am J Med ; 133(6): e280-e289, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32173347

RESUMO

BACKGROUND: Outcome postponement has been proposed as an effect measure for preventive drug treatment. It describes the average delay of the investigated unwanted clinical event, achieved by taking medication. The objective was to estimate postponement of death for the following heart failure medications compared to placebo: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), ARB added to ACE inhibitors, aldosterone antagonists, ivabradine, and renin antagonists. METHODS: We searched Medline and Embase from inception of databases until October 2017. Eligibility criteria were randomized placebo-controlled heart failure trials, including at least 1000 participants, with survival as a prespecified outcome and a minimum trial duration of 1 year. We calculated the outcome postponement by modeling the area between survival curves. This area was modeled on the basis of the hazard ratio or relative risk, the rate of mortality in the placebo group, and the trial duration. All results were standardized to a 3-year trial duration to ensure comparability between treatments. RESULTS: We identified 14 eligible trials, with a total of 52,014 patients. The results in terms of postponement of all-cause mortality was: beta-blockers 43.7 days (95% confidence interval [95% CI], 20.8-66.5), ACE inhibitors 41.0 days (95% CI, 18.8-63.3), and aldosterone-antagonists 41.3 days (95% CI, 14.3,68.4). CONCLUSION: The modeled outcome postponement estimates reiterate beta-blockers, ACE inhibitors, and aldosterone antagonists as the mainstay of heart failure treatment. Furthermore, ivabradine or ARBs added to ACE inhibitors results in no statistically significant gain in survival.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Taxa de Sobrevida , Causas de Morte , Quimioterapia Combinada , Insuficiência Cardíaca/mortalidade , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
BMJ Case Rep ; 13(1)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31969397

RESUMO

Muscular dystrophies are a heterogeneous group of disorders that commonly involve cardiac and skeletal muscle. Comprehensive guidelines for the management of cardiac failure and arrhythmias are available. However, the studies from which their recommendations are derived did not include any patients with muscular dystrophy. Some medications (eg, betablockers) may have significant side effects in this cohort. In some situations the use of agents with unique mechanisms of action such as ivabradine (a 'funny' channel inhibitor) may be more appropriate. Use of ivabradine has not previously been reported in limb girdle muscular dystrophy (LGMD). We describe the course of a patient with LGMD type 2I, cardiomyopathy and inappropriate sinus tachycardia treated with ivabradine. As advances in respiratory support have improved the outcomes of patients with muscular dystrophy; the prognostic significance of cardiac disease has increased. Ivabradine is tolerated and may reduce symptoms, morbidity and mortality in this cohort.


Assuntos
Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/etiologia , Ivabradina/uso terapêutico , Distrofia Muscular do Cíngulo dos Membros/complicações , Taquicardia Sinusal/tratamento farmacológico , Taquicardia Sinusal/etiologia , Antiarrítmicos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Metoprolol/uso terapêutico , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...